M2 Inhibitors
5 drugsAbout M2
The M2 receptor (CHRM2) is a muscarinic acetylcholine receptor involved in physiological processes like smooth muscle contraction. As a G protein-coupled receptor, it mediates the effects of acetylcholine in various tissues. Its activation impacts functions ranging from heart rate to glandular secretion.
Human genetics provide moderate support for M2 as a drug target, with a max genetic score of 0.56 linked to risk-taking behaviour. Variants in CHRM2 are associated with 35 diseases, including hypertrophic cardiomyopathy (0.52) and rheumatoid arthritis (0.48). Strong eQTL/pQTL signals further support its role in disease.
M2 is targeted by 5 FDA-approved drugs, all of which are small molecules, including INCRUSE ELLIPTA, SPIRIVA RESPIMAT and YUPELRI. Four drugs are for respiratory conditions, while one (DARIFENACIN HYDROBROMIDE) addresses other therapeutic areas. GSK and Boehringer Ingelheim are key players.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 1 trials.
M2 Genetic Evidence Moderate
Genetic evidence offers moderate support for M2, with a maximum score of 0.56.
Further research is needed to validate M2 as a target for genetically-supported indications.
Evidence Across Diseases
20 totalGWAS and other genetic studies link CHRM2 to 35 diseases.
🔗 Colocalization Evidence 5 strong
max H4: 1.00eQTL/pQTL signals for CHRM2 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top M2 Drugs
Five companies have approved drugs targeting M2, including GSK and Boehringer Ingelheim.
The presence of multiple players suggests moderate competition, requiring strong IP to succeed.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| YUPELRI | Viatris | 2018 | 1 |
M2 Drug Modality Landscape
Modalities
Routes of Administration
M2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide differentiation.
M2 Clinical Trials 174 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 19 | 17 | 0 | 2 | 100% |
| Phase 2 | 34 | 30 | 4 | 0 | 88% |
| Phase 3 | 68 | 66 | 2 | 0 | 97% |
| Phase 4 | 53 | 45 | 6 | 2 | 88% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
M2 Drug Approval Timeline (2012 - 2023)
The approval timeline spans 7 years, from 2012 (TUDORZA PRESSAIR) to 2018 (YUPELRI).
The recent approval of YUPELRI suggests continued interest in M2, but market saturation may be a concern.
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Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 144 clinical trials targeting M2.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities